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Anti-Malaria Drug Synthesised with Oxygen and Light

Anti-Malaria Drug Synthesised with Oxygen and Light

Photo: François Lévesque of MPG

There is an effective treatment against malaria, but it is not accessible to all of the more than 200 million people worldwide who are affected by the disease. Millions, especially in the developing world, cannot afford the combination drug preparation, which consists mainly of artemisinin. This may be about to change. Professor Peter H. Seeberger and his colleague François Lévesque have discovered a very simple way of synthesising the artemisinin molecule, which is known as an anti-malaria drug from traditional Chinese medicine and has an extremely complex chemical structure.

“The production of the drug is therefore no longer dependent on obtaining the active ingredient from plants,” says Seeberger.
As a starting point, the chemists use artemisinic acid – a substance produced as a hitherto unused by-product from the isolation of artemisinin from sweet wormwood, which is produced in volumes ten times greater than the active ingredient itself. Moreover, artemisinic acid can easily be produced in genetically modified yeast as it has a much simpler structure. “We convert the artemisinic acid into artemisinin in a single step,” says Seeberger. “And we have developed a simple apparatus for this process, which enables the production of large volumes of the substance under very controlled conditions.” The only reaction sequence known up to now required several steps, following each of which the intermediate products had to be isolated laboriously – a method that was far too expensive to offer as a viable alternative to the production of the drug from plants.

The striking simplification of artemisinin synthesis required not only a keen sense for an elegant combination of the correct partial reactions to enable the process to take place in a single step; it also took a degree of courage, as the chemists departed from the paths typically taken by industry up to now. The effect of the molecule, which not only targets malaria but possibly also other infections and even breast cancer, is due to, among other things, a very reactive chemical group formed by two neighbouring oxygen atoms – which chemists refer to as an endoperoxide. Seeberger and Lévesque use photochemistry to incorporate this structural element into the artemisinic acid. Ultraviolet light converts oxygen into a form that can react with molecules to form peroxides.

“We assume that 800 of our simple photoreactors would suffice to cover the global requirement for artemisinin,” says Seeberger. And it could all happen very quickly. Seeberger estimates that the innovative synthesis process could be ready for technical use in a matter of six months. This would alleviate the global shortage of artemisinin and exert considerable downward pressure on the price of the associated drugs.; Source: Max Planck Institute of Colloids and Interfaces


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